4866-57-3Relevant articles and documents
Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors
Makhaeva, Galina F.,Boltneva, Natalia P.,Lushchekina, Sofya V.,Serebryakova, Olga G.,Stupina, Tatyana S.,Terentiev, Alexey A.,Serkov, Igor V.,Proshin, Alexey N.,Bachurin, Sergey O.,Richardson, Rudy J.
, p. 1050 - 1062 (2016/02/19)
A series of 31 N,N-disubstituted 2-amino-5-halomethyl-2-thiazolines was designed, synthesized, and evaluated for inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE). The compounds did not inhibit AChE; the most active compounds inhibited BChE and CaE with IC50 values of 0.22-2.3 μM. Pyridine-containing compounds were more selective toward BChE; compounds with the para-OMe substituent in one of the two dibenzyl fragments were more selective toward CaE. Iodinated derivatives were more effective BChE inhibitors than brominated ones, while there was no influence of halogen type on CaE inhibition. Inhibition kinetics for the 9 most active compounds indicated non-competitive inhibition of CaE and varied mechanisms (competitive, non-competitive, or mixed-type) for inhibition of BChE. Docking simulations predicted key binding interactions of compounds with BChE and CaE and revealed that the best docked positions in BChE were at the bottom of the gorge in close proximity to the catalytic residues in the active site. In contrast, the best binding positions for CaE were clustered rather far from the active site at the top of the gorge. Thus, the docking results provided insight into differences in kinetic mechanisms and inhibitor activities of the tested compounds. A cytotoxicity test using the MTT assay showed that within solubility limits (30 μM), none of the tested compounds significantly affected viability of human fetal mesenchymal stem cells. The results indicate that a new series of N,N-disubstituted 2-aminothiazolines could serve as BChE and CaE inhibitors for potential medicinal applications.
One pot synthesis using supported reagents system KSCN/SiO 2-RNH3OAc/Al2O3: Synthesis of 2-aminothiazoles and N-allylthioureas
Aoyama, Tadashi,Murata, Sumiko,Arai, Izumi,Araki, Natsumi,Takido, Toshio,Suzuki, Yoshitada,Kodomari, Mitsuo
, p. 3201 - 3213 (2007/10/03)
A simple and efficient method has been developed for the synthesis of 2-aminothiazoles and N-allylthioureas from commercially available materials in one pot by using a supported reagents system, KSCN/SiO2-RNH 3OAc/Al2O3, in which α-halo ketone reacts first KSCN/SiO2 and the product, α-thiocyanatoketone, reacts with RNH3OAc/Al2O3 to give the final product, 2-aminothiazoles, in good yield and allyl bromide reacts with KSCN/SiO 2 and the product, allyl isothiocyanate, reacts with RNH 3OAc/Al2O3 to give N-allylthiourea.
One-pot synthesis of N-allylthioureas using supported reagents
Aoyama, Tadashi,Murata, Sumiko,Nagata, Yasutaka,Takido, Toshio,Kodomari, Mitsuo
, p. 4875 - 4878 (2007/10/03)
A simple and efficient method has been developed for the synthesis of N-allylthioureas from allylic bromides in one-pot by using a supported reagents system, KSCN/SiO2-RNH3OAc/Al2O3, in which allyl bromide reacts first with KSCN/SiO2 and the product, allyl isothiocyanate, reacts with RNH3OAc/Al2O3 to give the final product, N-allylthiourea, in good yield.
